Catechol-degrading enzyme

A chlorophenoxyacetate-degrading Arthrobacter sp. contained an enzyme, which converted 2,4-dichlorophenol and other chlorophenols to catechols. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) and Oj were required for the reaction. The enzyme hydroaylating 2,4-dichlorophenol was partially separated from the catechol-degrading enzyme present in the bacterial extract. The compotmds formed from... 

After reuptake into the cytosol, some noradrenaline may be taken up into the storage vesicles by the vesicular transporter and stored in the vesicles for subsequent release (see above). However, it is thought that the majority is broken down within the cytosol of the nerve terminal by monoamine oxidase (MAO ECl.4.3.4). A second degradative enzyme, catechol-O-methyl transferase (COMT EC2.1.1.6), is found mostly in nonneuronal tissues, such as smooth muscle, endothelial cells or glia. The metabolic pathway for noradrenaline follows a complex sequence of alternatives because the metabolic product of each of these enzymes can act as a substrate for the other (Fig 8.8). This could enable one of these enzymes to compensate for a deficiency in the other to some extent. 

Further details of the pathways for the degradation of PAFIs are described in Chapter 6, Section 6.2.1 and in a review (Neilson and Allard 1998). It seems that most of the degradative enzymes are inducible, and this is consistent with the fact that most strains have been isolated after specific enrichment with the xenobiotic. The case of the partially constitutive synthesis of catechol 1,2-dioxygenase in the yeast Trichosporon cutaneum (Shoda and Udaka 1980) has been noted (Section 4.5.2). In the case of biotransformation, however, there are sporadic examples of the constitutive synthesis of enzymes. For example, the system carrying out the O-methylation of halogenated phenolic compounds was apparently constitutive (Neilson et al. 1988) this observation is consistent with the isolation of the strains by enrichment with Q compounds structurally unrelated to the halogenated substrates. The O-methylation reaction may function primarily as a detoxification system, so that in this case constitutive synthesis of the enzyme would clearly be advantageous to the survival of the cells. 

Although the liver is the body s principal centre for metabolic degradation, this process also goes on elsewhere. For example the bloodstream carries non-specific esterases which rapidly hydrolyse almost every kind of ester, natural or fabricated, and they are accompanied by a rather less active nonspecific amidase. Many degradative enzymes operate in the bowel-wall and the kidney. An inactivator of catecholamines, catechol 0-methyltransferase, is found in many tissues, and Section 12.5 describes the enzyme that hydrolyses acetylcholine in the neuromuscular junction. 

The degradation of lAA can be brought about by light, particularly UV, in the presence of catalysts such as riboflavin, and by enzymes. Peroxidases which are known as lAA oxidases rank among the lAA degrading enzymes. They require Mn -+ and monophenols such as / -hydrox-ybenzoic acid or the flavonole kaempferol as cofactors. o-Diphenols such as catechol or the flavonole quercetin are inhibitors of many lAA oxidases. Perhaps one of the physiological functions of the flavonoles lies in this regulation of the activity of lAA oxidases. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

This comprises a heterogeneons gronp of enzymes that is used for the degradation of snbstrates including gentisate, salicylate, and l-hydroxynaphthalene-2-carboxylate by pathways that do not involve catechols ... 

Burkholderia cepacia strain 2CBS is able to degrade ort/jo-halogenated benzoates by dioxygenation to catechol with the elimination of halide and decarboxylation. The enzyme contains a ferredoxin-and a Rieske-type [2Fe-2S] center. These could be distinguished on the basis of their EPR spectra, and the results were compared with those for other [2Fe-2S] clusters (Riedel et al. 1995). 

The mandelate pathway in Pseudomonas putida involves successive oxidation to benzoyl formate and benzoate, which is further metabolized via catechol and the 3-ketoadipate pathway (Figure 8.35a) (Hegeman 1966). Both enantiomers of mandelate were degraded through the activity of a mandelate racemase (Hegeman 1966), and the racemase (mdlA) is encoded in an operon that includes the next two enzymes in the pathway—5-mandel-ate dehydrogenase (mdlB) and benzoylformate decarboxylase (mdlC) (Tsou et al. 1990). 

Aerobic degradation of chlorinated arene hydrocarbons, including the important group PCBs, and chlorobenzoates that are produced from them as metabolites, is generally initiated by dihy-droxylation of the rings to dihydrodiols followed by dehydrogenation to catechols. Halide may be lost simultaneously and for 2-halogenated benzoates, both halide and carboxyl. Salient aspects are summarized, and attention drawn to selected aspects of enzyme inhibition. 

The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its components choline and acetate it is one of the fastest acting enzymes in the body and acetylcholine removal occurs in less than 1 msec. The most important mechanism for removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic neuron that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines — epinephrine and norepinephrine — are inactivated by catechol-O-methyltransferase (COMT) in the liver. 

An enzymatic pathway for indole degradation was found in A. niger, inducible by the substrate within a 5-h period during growth. Among the enzymes found, anthranilate hydroxylase, N-formylanthranilate deformylase, 2,3-dihydroxybenzoate decarboxylase, and catechol dioxygenase were isolated, and their activities were demonstrated in a cell-free system [342],... 

---